Is trimethoprim/sulfamethoxazole-associated increase in serum creatinine a pseudo-elevation or true nephrotoxicity?

Urakami, Toshiharu; Hamada, Yohei; Oka, Yoshikazu; Kannae, Mikinori; Okinaka, Tomohide; Sanada, Ayaka; Shimanoe, Chisato; Aoki, Yosuke

doi:10.1016/j.jiac.2021.03.015

Cited by 7 publications

(6 citation statements)

References 23 publications

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“…In fact, in patients whose renal function was assessed based on eGFR Cys-C and eGFR SCr , attention should be paid to TMP-SMXinduced nephrotoxicity and pseudo-elevation. 36 Unfortunately, no patients in this study had their Cys-C levels measured before or after initiation of TMP-SMX treatment. However, we excluded the effects of drugs other than TMP on the increase in the SCr concentration as much as possible.…”

Section: Resultsmentioning

confidence: 94%

“…Therefore, it may be useful to evaluate the effects of TMP‐SMX on the secretion of SCr from proximal tubules by using eGFR Cys‐C as an indicator. In fact, in patients whose renal function was assessed based on eGFR Cys‐C and eGFR SCr , attention should be paid to TMP‐SMX‐induced nephrotoxicity and pseudo‐elevation 36 . Unfortunately, no patients in this study had their Cys‐C levels measured before or after initiation of TMP‐SMX treatment.…”

Section: Discussionmentioning

confidence: 95%

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Impact of trimethoprim on serum creatinine, sodium, and potassium concentrations in patients taking trimethoprim‐sulfamethoxazole without changes in glomerular filtration rate

Yokoyama

Nakagawa

Aiuchi

et al. 2022

Clinical Pharmacy Therapeu

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What is known and objective: Trimethoprim (TMP) inhibits the Na + /K + -ATPase present in the basement membrane of distal tubular epithelial cells. However, hyponatremia and hyperkalemia may develop in patients taking TMP-sulfamethoxazole (SMX). In addition, because TMP inhibits drug transporters, such as organic cation transporter 2 and multidrug and toxin extrusion protein 2-K in proximal tubules, reversible increases in the concentration of serum creatinine (SCr), the substrate of these transporters, may occur. Here, we investigated variability in SCr, serum sodium (Na + ), and serum potassium (K + ) concentrations after initiation of TMP-SMX treatment and evaluated the risk of hyponatremia and hyperkalemia in patients with increased SCr concentrations without changes in the glomerular filtration rate (GFR).Methods: In this retrospective study, all patients aged 20 years or older who received oral TMP-SMX during hospitalization were enrolled. The patients with estimated creatinine (Cr) clearance (eCCr) lower than 30 mL/min were excluded, as were patients taking drugs that were likely to induce renal dysfunction, drugs other than glucocorticoids that were likely to induce electrolyte imbalances, or drugs other than TMP that inhibit tubular Cr secretion. Additionally, those with SCr concentrations elevated more than 30% from baseline or serum blood urea nitrogen concentration levels above 20 mg/dL during follow-up were also excluded.Results and Discussion: In total, 111 patients were enrolled in the study. The common independent variable affecting the change rate in SCr, Na + , and K + concentrations (ΔSCr, ΔNa + , and ΔK + ) from baseline to the highest value during the follow-up period (14 days after initiation of TMP-SMX treatment) was the daily dose of TMP.There were significant correlations between ΔSCr and ΔNa + or ΔK + (ρ = À0.199, p = 0.036 and ρ = 0.244, p = 0.010, respectively). Kaplan-Meier curves for hyponatremia and hyperkalemia with greater than or equal to grade 1 severity showed different profiles when the TMP dose varied (≤ 160 vs. > 160 mg/day; p = 0.005 and 0.008). The cumulative incidences of both adverse effects were 64.7% (median: 7 days) and 29.4% in patients taking more than 160 mg/day TMP and 35.2% and 6.7% in patients taking 160 mg/day TMP or less. Thus, TMP may affect the kinetics of Cr, Na + , and K + in the proximal and distal tubules in a dose-dependent without changing the GFR.

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Section: Resultsmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 95%

Impact of trimethoprim on serum creatinine, sodium, and potassium concentrations in patients taking trimethoprim‐sulfamethoxazole without changes in glomerular filtration rate

Yokoyama

Nakagawa

Aiuchi

et al. 2022

Clinical Pharmacy Therapeu

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“…10 In cases where a serum creatinine rise is observed after sulfamethoxazole/trimethoprim exposure, it is challenging to differentiate true nephrotoxicity from pseudonephrotoxicity. 23 Observed rises in serum creatinine after exposure to piperacillin/tazobactam in combination with vancomycin may also be attributable, at least in part, to interactions with creatinine at tubular transporters. 24 A framework has been proposed to include novel kidney biomarkers in the evaluation of nephrotoxic AKI that may differentiate true nephrotoxicity from pseudonephrotoxicity.…”

Section: Medication Management In Aki Without Krtmentioning

confidence: 99%

Medication Management in the Critically Ill Patient with Acute Kidney Injury

Behal

Flannery

Barreto

2023

CJASN

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AKI occurs frequently in critically ill patients. Patients with AKI, including those who require KRT, experience multiple pharmacokinetic and pharmacodynamic perturbations that dynamically influence medication effectiveness and safety. Patients with AKI may experience both subtherapeutic drug concentrations, which lead to ineffective therapy, and supratherapeutic drug concentrations, which increase the risk for toxicity. In critically ill patients with AKI not requiring KRT, conventional GFR estimation equations, especially those based on serum creatinine, have several limitations that can limit the accuracy when used for medication dosing. Alternative methods to estimate kidney function may be informative, including use of measured urinary creatinine clearance, kinetic eGFR, and equations that integrate novel kidney biomarkers. For critically ill patients with AKI requiring KRT, physicochemical properties of the drug, the KRT prescription and circuit configuration, and patient-specific factors each contribute to medication clearance. Evidence-based guidance for medication dosing during AKI requiring KRT is often limited. A working knowledge of the basic tenets of drug elimination during KRT can provide a framework for how to approach decision making when the literature is lacking. Iterative re-evaluation of a patient's progress toward therapeutic goals with a medication must occur over the arc of critical illness, including and especially in the setting of dynamic kidney function.

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“…Together with adequate antibiotic therapy, surgical interventions are mandatory in necrotizing fasciitis and surgical or computed tomography (CT)-guided drainage are essential in draining abscesses for successful outcomes [1]. Traditional treatment options have been associated with various toxicities such as nephrotoxicity for trimethoprim-sulfamethoxazole (TMP/SMX) and vancomycin [13,14], Clostridium difficile colitis for clindamycin [15] and gastrointestinal disturbance for doxycycline [16].…”

Section: Introductionmentioning

confidence: 99%

New drugs for methicillin-resistant Staphylococcus aureus skin and soft tissue infections

Hindy

Haddad

Kanj

2021

Current Opinion in Infectious Diseases

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Purpose of reviewStaphylococcus aureus is a pathogen incriminated in skin and soft tissue infections (SSTIs), with methicillinresistant S. aureus (MRSA) becoming the predominant cause and representing a significant burden to the healthcare system. The last updated Infectious Diseases Society of America (IDSA) guidelines concerning MRSA infections and SSTIs management were published in 2011 and 2014, respectively. The UK updated guidelines for MRSA infection treatment were published in 2021. Older treatment options may be associated with toxicity and require frequent dosing. There is a paucity of recent reviews on the armamentarium of new agents for MRSA SSTIs treatment. Recent findingsSince 2005, several new antibiotics received a fast-track approval by the Food and Drug Administration (FDA) for SSTI treatment. These drugs include delafloxacin, omadacycline, tedizolid, ceftaroline, dalbavancin, oritavancin and telavancin. In this manuscript, we will review the data that led to these new drugs approval and discuss their advantages and disadvantages in MRSA SSTIs management. SummaryMRSA is a major cause of SSTIs. Several novel therapies covering MRSA were FDA-approved for SSTIs. However, the current IDSA guidelines for MRSA infection and SSTIs as well as the recently published UK guidelines on MRSA treatment only consider these drugs as alternative choices or do not mention them at all. Keywordsacute bacterial skin and skin structure infections, methicillin-resistant Staphylococcus aureus, skin and soft tissue infections admissions for SSTIs was increasing by 30% from 2000 to 2004, a more recent study showed a decrease of 15.8% in MRSA-related hospitalizations between 2010 and 2014 [7,8].Historically, community-acquired MRSA (CA-MRSA) was genetically different from hospitalacquired-MRSA (HA-MRSA) and could be clinically differentiated because it was essentially causing limited to uncomplicated SSTIs [9]. However, the

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Is trimethoprim/sulfamethoxazole-associated increase in serum creatinine a pseudo-elevation or true nephrotoxicity?

Cited by 7 publications

References 23 publications

Impact of trimethoprim on serum creatinine, sodium, and potassium concentrations in patients taking trimethoprim‐sulfamethoxazole without changes in glomerular filtration rate

Impact of trimethoprim on serum creatinine, sodium, and potassium concentrations in patients taking trimethoprim‐sulfamethoxazole without changes in glomerular filtration rate

Medication Management in the Critically Ill Patient with Acute Kidney Injury

New drugs for methicillin-resistant Staphylococcus aureus skin and soft tissue infections

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